Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host–microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host–microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.
Source: Gut Microbes
Authors: Capucine Durand, Laurye-Anne Eveillard, Mathilde Labouret, Florence Aeschlimann, Alexandre Belot, Karine Brochard, Benoit Chassaing, Priscilla Boizeau, Rym Boulkedid, Aurélia Carbasse, Bilade Cherqaoui, Cécile Dumaine, Anne Dumay, Cécile Frachette, Véronique Hentgen, Cécile Kedzia, Therese Kolta, Isabelle Koné-Paut, Quentin Lamy-Besnier, Sophie Guilmin-Crepon, Lara Lima-Antoine, Pascal Pillet, Pierre Quartier, Stéphanie Tellier, Julien Tourneur-Marsille, Heloise Reumaux, Caroline Vinit, Emilie Viennois, Ulrich Meinzer
Institutions: Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Centre de Recherche sur l'Inflammation, Hôpital Necker-Enfants Malades, University Hospital of Basel, Institut Necker Enfants Malades, University Children’s Hospital Basel, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Centre International de Recherche en Infectiologie, Institut Pasteur, Centre d'Investigation Clinique Robert Debré, Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Hôpital Ambroise-Paré, Infection et inflammation, Centre de Référence des Maladies Autoinflammatoires et des Amyloses, Bicêtre Hospital, Centre Hospitalier Universitaire de Bordeaux, Université de Lille, Hôpital Jeanne de Flandre
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,060
Awards: G3186420570, G4180218856, G4422322373, G5420063140, Translational investigation of the pathophysiological role of intestinal barrier dysfunction and microbiota in juvenile idiopathic arthritis, Peptidoglycome-based gut microbiome analysis applied to Juvenile Idiopathic Arthritis., G6516395363, G7199963277
OpenAlex ID: W7212179104